The diagnosis and management of glaucoma require sensitive methods for detecting and measuring damage to retinal ganglion cells and their axons. New quantitative methods for optically assessing the retinal nerve fiber layer (RNFL) have begun to deliver enhanced sensitivity and objectivity over previous methods and are moving toward routine clinical use. The long-term objectives of this continuation project are a) to provide a comprehensive, quantitative, basic understanding of the optical properties of the RNFL and b) to translate this basic knowledge into practical improvements in clinical assessment of glaucomatous damage. Imaging micropolarimetry, scanning laser polarimetry and optical coherence tomography will be used to pursue the following Specific Aims: 1) Identify the cylindrical structures responsible for the optical properties of the RNFL by characterizing their physical and biological properties. The RNFL behaves as a uniform thick array of approximately parallel light scattering cylinders embedded in a birefringent slab. Reflectance spectra suggest two cylindrical mechanisms, one thin relative to the wavelength and the other thicker. The identities of the cylinders and the mechanism for RNFL birefringence will be determined. 2) Test in vitro three hypotheses about the relation between RNFL birefringence and the structure of nerve fiber bundles. 3) Measure and map RNFL birefringence in humans as a basis for "tissue diagnosis" of the RNFL. Birefringence is an intrinsic property of the tissue, depends directly on RNFL ultrastructure, and may provide a means of early detection of structural damage to ganglion cells in glaucoma.